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Journal of Pharmacology and Experimental Therapeutics

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OtherTOXICOLOGY

The Long-Acting Parenteral Iron Chelator, Hydroxyethyl Starch-Deferoxamine, Fails to Protect against Alcohol-Induced Liver Injury in Rats

S. M. Hossein Sadrzadeh, Philip E. Hallaway and Amin A. Nanji
Journal of Pharmacology and Experimental Therapeutics February 1997, 280 (2) 1038-1042;
S. M. Hossein Sadrzadeh
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Philip E. Hallaway
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Amin A. Nanji
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Abstract

We studied the effect of the long-acting parenteral iron chelator, hydroxyethyl starch deferoxamine (HES-DFO) on liver nonheme iron, lipid peroxidation and pathologic changes in the liver in the intragastric feeding rat model for alcoholic liver disease. Male Wistar rats (225–250 g) were fed liquid diet and ethanol for 2 months. In control pair-fed animals, ethanol was isocalorically replaced by dextrose. Two additional groups of animals (dextrose and ethanol fed) received HES-DFO (25 mg deferoxamine equivalents/kg, three times a week). The blood ethanol level in the ethanol-fed animals was maintained between 150 and 350 mg/dl. For each animal, the levels of hepatic nonheme iron, lipid peroxidation and pathologic changes were evaluated. Ethanol administration caused fatty liver, necrosis and inflammation. Addition of HES-DFO to the ethanol diet increased the severity of pathologic changes, particularly necrosis and inflammation. The nonheme iron in alcohol-fed animals was significantly higher (18.3 ± 4.3 μg liver) than in pair-fed dextrose controls (12.5 ± 1.5 μg, P < .05). Addition of HES-DFO significantly increased nonheme iron levels in the dextrose-fed rats (17.1 ± 2.0 μg/g, P < .02) but not in ethanol-fed rats (20.0 ± 2.0). Ethanol increased levels of conjugated dienes; these levels were not altered by HES-DFO. The most significant observations in this study were: 1) the higher hepatic nonheme iron content in ethanol-fed rats compared with pair-fed dextrose controls; 2) the absence of changes in hepatic nonheme iron levels or lipid peroxidation in ethanol-fed groups treated with HES-DFO; and 3) the worsening of liver injury in ethanol-fed rats by HES-DFO.

Footnotes

  • Send reprint requests to: Dr. S.M. Hossein Sadrzadeh, Dept of Pathology, M323, Beth Israel Deaconess Medical Center, One Deaconess Road, Boston, MA 02215.

  • Abbreviations:
    ALD
    alcoholic liver disease
    ALT
    alanine aminotransferase, DFO, deferoxamine
    HES
    hydroxyethyl starch
    • Received July 29, 1996.
    • Accepted October 7, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 280, Issue 2
1 Feb 1997
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OtherTOXICOLOGY

The Long-Acting Parenteral Iron Chelator, Hydroxyethyl Starch-Deferoxamine, Fails to Protect against Alcohol-Induced Liver Injury in Rats

S. M. Hossein Sadrzadeh, Philip E. Hallaway and Amin A. Nanji
Journal of Pharmacology and Experimental Therapeutics February 1, 1997, 280 (2) 1038-1042;

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OtherTOXICOLOGY

The Long-Acting Parenteral Iron Chelator, Hydroxyethyl Starch-Deferoxamine, Fails to Protect against Alcohol-Induced Liver Injury in Rats

S. M. Hossein Sadrzadeh, Philip E. Hallaway and Amin A. Nanji
Journal of Pharmacology and Experimental Therapeutics February 1, 1997, 280 (2) 1038-1042;
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